Transketolase (TKT) is a key metabolic enzyme in the non‑oxidative phase of the pentose phosphate pathway and is highly conserved across prokaryotes and eukaryotes. It catalyzes two reversible reactions that mediate the interconversion of phosphorylated sugars from three to seven carbons. Although TKT exhibits broad tissue distribution in mammals and is frequently upregulated across diverse malignancies, its definitive physiological roles and pathological implications remain mechanistically unresolved. Recent studies have shown that obesity and metabolic diseases, such as fatty liver disease,are characterized by hyperinsulinemia‑induced insulin resistance, with high insulin levels inducing TKT upregulation. As a master regulator of cellular pentose phosphate flux, TKT channels pentose‑containing metabolites into glycolytic processing, thereby accelerating pentose phosphate catabolism and reducing nucleoside and nucleotide pools. Emerging research has elucidated the roles of TKT in hepatocytes, adipocytes, regulatory T cells, and hepatocellular carcinoma, emphasizing its emerging role in pentose catabolism to coordinate nucleoside homeostasis with mitochondrial function, modulate nucleotide availability and genomic stability, and influence mitochondrial metabolite levels linked to DNA methylation. Collectively, these findings point to TKT as a promising metabolic target, offering novel preventive and therapeutic avenues for obesity, fatty liver disease, and hepatocellular carcinoma.

Objective ·To combine the Cre/loxP recombinase system with a tooth extraction model to explore the spatiotemporal distribution of Col1⁺ cells secreting type Ⅰ collagen (collagen type Ⅰ, COL1) during alveolar socket healing and their potential to differentiate into osteoblasts. Methods ·Col1-CreERT2 mice were mated with Rosa26-LoxP-Stop-LoxP-tdTomato mice to obtain Col1-CreERT2;tdTomato double transgenic offspring mice. Fifteen offspring mice were selected and tamoxifen (TA) was intraperitoneally injected to label the Col1⁺ cell lineage. One week later, the right maxillary first molars of the offspring mice were completely extracted under general anesthesia to establish a double transgenic mouse tooth extraction model. The offspring mice were divided into 5 groups, with 3 mice in each group. Maxillary bone samples were collected at 0, 3, 7, 14, and 28 days after tooth extraction, respectively. Paraffin sections were used to observe the dynamic distribution of the Col1⁺ cell lineage during alveolar socket healing. Immunofluorescence techniques were employed to label the osteoblast-specific transcription factor osterix (OSX), vascular marker endomucin (EMCN), and neuronal marker β3-tubulin to investigate the osteogenic potential of Col1⁺ cells and their spatial localization relationship with blood vessels and nerves. Results ·The tooth extraction model of Col1-CreERT2;tdTomato double transgenic mice was successfully established. Paraffin section observations revealed that Col1⁺ cells appeared in the alveolar socket on the third day after the model was established; on the seventh day, the number of Col1⁺ cells increased and alveolar socket osteogenesis gradually occurred; on the 28th day, the proportion of Col1⁺ cells further increased and they were distributed around the bone trabeculae. The results of statistical analysis showed that the number of Col1⁺ cells increased over time during alveolar socket healing (all P<0.001, compared with day 0). The results of Immunofluorescence assay indicated that the number of Col1⁺ OSX⁺ double-positive cells in the alveolar socket gradually increased from the 7th to the 28th day after the model was established, and Col1⁺ cells were spatially adjacent to EMCN and β3-tubulin. Conclusion ·During alveolar socket healing, Col1⁺ cells have the potential to differentiate into osteoblasts, and may also be involved in the formation of blood vessels and nerves.

Objective ·To investigate the regulation of zinc finger protein 668 (ZNF668) expression in head and neck squamous cell carcinoma (HNSCC) by histone lysine lactylation (Kla), and to elucidate the molecular mechanisms by which ZNF668 promotes the proliferation of HNSCC cells. Methods ·Multiplex immunofluorescence was used to detect pan-lysine lactylation (PKla) levels in tissue microarrays (TMAs) constructed from HNSCC and adjacent normal oral mucosal tissues, and the correlation between PKla expression and clinicopathological characteristics was analyzed. Western blotting was performed to identify specific sites where exogenous lactate treatment regulated Kla in HNSCC cells. CUT&Tag technology was utilized to screen histone lactylation-related and open chromatin genes. These data were combined with RNA sequencing (RNA-seq) experiments to detect differentially expressed downstream genes stimulated by lactate at the transcriptome level, and to screen specific downstream target genes regulated by Kla. Chromatin immunoprecipitation (ChIP) assays were used to verify the accessibility of Kla to downstream target genes. Western blotting was used to analyze the expression levels of ZNF668 in human normal oral keratinocytes (NOK) and HNSCC cells. The expression of ZNF668 mRNA in NOK and HNSCC cells was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting was used to detect the expression of the most sensitive modification site to lactate stimulation and ZNF668 under control treatments with or without lactate. The 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assays were used to analyze the effects of knocking down ZNF668 on the proliferation ability of HNSCC cells. Western blotting was used to analyze the expression of WNT3A (wingless-type MMTV integration site family member 3A), β-catenin, and G1/S-specific cyclin-D1 (CCND1) proteins after knocking down ZNF668. Immunohistochemistry (IHC) was used to detect the expression of ZNF668 and cell proliferation in the subcutaneous tumors of nude mice stimulated by lactate. Results ·Multiplex immunofluorescence results indicated that the level of PKla modification in HNSCC tissues was higher than that in normal oral mucosa, and that a high level of lactylation modification was associated with advanced TNM stage. Western blotting results showed that lactate promoted Kla in HNSCC cells, and the Kla at the H3K9 site was the most significant. The results of CUT&Tag combined with RNA-seq screening and ChIP-PCR verification demonstrated that ZNF668 was one of the main downstream targets of H3K9la. Western blotting and qRT-PCR analyses showed that the expression level ofZNF668 in HNSCC cells was significantly higher than that in NOK cells, and that the expression of H3K9la and ZNF668 in HNSCC cells was positively correlated with lactate stimulation. After knocking down ZNF668 in HNSCC cells, the proliferative ability of the cells was significantly reduced compared to the control group. Meanwhile, the protein expressions of WNT3A, β-catenin, and CCND1 also showed a downward trend. The IHC assay demonstrated that lactate stimulation increased the expression of ZNF668 and promoted cell proliferation in subcutaneous tumors of nude mice. Conclusion ·Histone lysine lactylation promotes the expression of ZNF668, which plays a significant cancer-promoting role in HNSCC. ZNF668 can further regulate the proliferation of tumor cells by enhancing the expression level of the WNT3A/β-catenin/CCND1 signaling axis.

Objective ·To investigate the regulatory role of microglial transient receptor potential vanilloid 1 (TRPV1) in the pathological progression of apolipoprotein E4 (ApoE4)-associated Parkinson's disease (PD). Methods ·APOE3/Trpv1^flox/flox (E3/Trpv1^fl/fl), APOE4/Trpv1^flox/flox (E4/Trpv1^fl/fl), and microglia-specific Trpv1 knockout Cx3cr1^Cre (E4/Trpv1^MGKO) mice were bred and injected with human A53T α-synuclein (AAV-hα-syn) into the substantia nigra pars compacta (SNpc). AAV-GFP was injected into the SNpc of E3/Trpv1^fl/fl mice as a control. After 30 days, motor function, coordination, and muscle endurance were evaluated using the open field test, traction test, pole test, rotarod test, and tail suspension test, while spatial learning and memory were assessed using the Morris water maze test. The immunofluorescence technique was used. The survival of dopaminergic neurons and pathological α-syn deposition in the SNpc were detected using tyrosine hydroxylase (TH) and phosphorylated Ser129 α-synuclein [p-α-syn (Ser129)] antibodies. The phagocytosis of microglia in the midbrain was detected using ionized calcium-binding adapter molecule 1 (Iba1) co-staining with p-α-syn (Ser129), while the accumulation of lipid droplets in microglia, neurons, and astrocytes was observed by BODIPY 493/503 staining. Results ·In traction tests, E4/Trpv1^MGKO(AAV-hα-syn) mice showed no significant differences in grip strength compared to E4/Trpv1^fl/fl(AAV-hα-syn) group. However, these mice exhibited increased mean velocity and total distance in open field tests, significantly prolonged time to turn (t_turn) and time for lateral ambulation (t_LA) in pole tests, shortened latency to remain on the rotarod, and induced stronger dystonic postures during tail suspension, indicating aggravated motor dysfunction in ApoE4-associated PD mice. The Morris water maze demonstrated that E4/Trpv1^MGKO(AAV-hα-syn) mice exhibited significantly prolonged escape latency and a reduced proportion of travel distance in the target quadrant, indicating that TRPV1 deficiency in microglia significantly impaired spatial learning ability in ApoE4-associated PD mice. Immunofluorescence revealed that the loss of dopaminergic neurons in the SNpc was aggravated in E4/Trpv1^MGKO(AAV-hα-syn) mice, and the p-α-syn deposition in the SNpc was increased. The phagocytosis of microglia in the mesencephalon was enhanced, and the accumulation of lipid droplets was increased. However, the deficiency of TRPV1 in microglia did not aggravate the accumulation of lipid droplets in astrocytes and neurons. Conclusion ·TRPV1 deficiency in microglia accelerates the pathological progression of ApoE4-associated PD and disrupts lipid metabolic homeostasis in microglia.

Objective ·To compare pregnancy outcomes between broad-spectrum antibiotics administered after hysteroscopy and 16S rRNA gene sequencing combined with targeted antibiotics and Lactobacillus supplementation in patients with recurrent implantation failure (RIF) and chronic endometritis (CE). Methods ·This retrospective study analyzed 676 RIF patients who underwent either a 16S rRNA test during the mid-secretory phase or hysteroscopy during the proliferative phase at the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2023 to May 2025, after excluding known factors (preimplantation genetic testing for aneuploidies was not performed). Twenty-seven patients with 16S rRNA results indicating Lactobacillus abundance <90% and single-pathogen abundance≥10% were included in the 16S rRNA-diagnosed CE group (16S rRNA group). These patients received targeted antibiotics based on the pathogens for 7‒10 d, followed by vaginal Lactobacillus supplementation for 10 d. Sixty-five patients were diagnosed through hysteroscopic examination and CD138 immunohistochemical testing and were included in the hysteroscopy-diagnosed CE group (hysteroscopy group). They received levofloxacin combined with metronidazole for 14 d. All patients commenced frozen embryo transfer (FET) cycles in the subsequent menstrual cycle after treatment. Propensity score matching (1:4) was performed on FET cycles from the two groups using 13 covariates affecting pregnancy outcomes. The primary endpoint was the live birth rate. The secondary endpoints included the clinical pregnancy rate, human chorionic gonadotropin (HCG)-positive rate, miscarriage rate, and the incidences of pregnancy complications and neonatal adverse outcomes. Multivariate Logistic regression analysis was performed to assess potential risk factors affecting live birth. Results ·In the hysteroscopy group, 65 patients underwent 127 FET cycles, while in the 16S rRNA group, 27 patients underwent 33 FET cycles. Among them, 47 patients (74 FET cycles) from the hysteroscopy group and 22 patients (26 FET cycles) from the 16S rRNA group were successfully matched. After matching, the 16S rRNA group had significantly higher live birth rate (61.5% vs 23.0%, P=0.001), clinical pregnancy rate (65.4% vs 33.8%, P=0.011), and HCG-positive rate (73.1% vs 46.7%, P=0.038) than the hysteroscopy group. There were no significant differences in miscarriage rate, ectopic pregnancy rate, or the incidences of pregnancy complications and neonatal adverse outcomes between the two groups (all P>0.05). Multivariate Logistic regression analysis showed that the hysteroscopy group was associated with a lower live birth rate (OR=0.230, 95%CI 0.087‒0.607, P=0.003). Additionally, advanced maternal age, increased body mass index (BMI), transfer of only one embryo, and transfer of cleavage-stage embryos were all associated with a lower live birth rate (all P<0.05). Conclusion ·Compared with broad-spectrum antibiotics following hysteroscopy, 16S rRNA sequencing-based microbiota testing combined with targeted antibiotic therapy and Lactobacillus supplementation more effectively improves pregnancy outcomes in RIF patients with CE, and no adverse effects on maternal and fetal safety have been found.

Objective ·To investigate the correlation between obstructive sleep-disordered breathing (OSDB) and temporomandibular joint (TMJ) condylar resorption in adolescents. Methods ·From September 2018 to December 2023, consecutive adolescents (aged 10 to 19 years) who visited the TMJ Clinic at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were recruited in the present study. Patients were divided into the OSDB group and the non-OSDB group based on whether the frequency of snoring was ≥3 nights per week. Demographic information, history of upper airway-related diseases, tongue habits, and mouth-breathing habits were collected for both groups. The presence or absence of TMJ condylar absorption was assessed, and condylar height was measured. Intergroup differences in the above variables were compared. To further explore the association between various factors and OSDB, variables with statistical significance in the univariate analysis were included in a logistic regression model for multivariable analysis. Results ·A total of 439 adolescent patients were enrolled during the study period, including 30 cases in the OSDB group and 409 cases in the non-OSDB group. There was no significant difference in demographic information between the two groups (P>0.05). The proportions of patients with a history of adenoid and tonsil diseases and adverse tongue habits in the OSDB group were significantly higher than those in the non-OSDB group (P=0.001 and P=0.040, respectively). The incidence of TMJ condylar resorption was significantly higher in the OSDB group than that in the non-OSDB group (P=0.004), and condylar height in the OSDB group was significantly lower than that in the non-OSDB group (P<0.001). Multivariate logistic regression analysis revealed that condylar resorption (OR=4.837, 95%CI 1.889‒12.336, P<0.001) and decreased condylar height (OR=0.547, 95%CI 0.426‒0.678, P<0.001) were closely associated with the occurrence of OSDB. Conclusion ·These results suggest that TMJ condylar resorption is closely related to the occurrence of OSDB in adolescents.

Objective ·To explore the role of gestational weight gain (GWG) in the association between breastfeeding duration and offspring neurodevelopment, and to identify appropriate GWG to sustain breastfeeding among reproductive-age women. Methods ·A prospective birth cohort study was conducted in Shanghai from 2010 to 2012. Mothers were recruited during mid- to late pregnancy and followed up until 24‒36 months postpartum, and information on GWG, breastfeeding duration, and related confounders was collected. Toddler neurodevelopment was assessed by the developmental quotient (DQ) of the Gesell Developmental Schedules (GDS) and scores from the Chinese Toddler Temperament Scale (CTTS). Two-piece-wise linear regression analyses were conducted (due to non-linear relationships) on the associations between breastfeeding duration and toddler neurodevelopment under different GWG stratifications, and between GWG and breastfeeding duration. Results ·A total of 225 mother-infant pairs were included in this study, and the mean breastfeeding duration was 7.4 months. After adjustment for related confounders, significant differences in the associations of breastfeeding duration with neurodevelopment were observed among mother-child pairs under different GWG stratifications. For pairs with excessive GWG, when breastfeeding duration was <6 months, longer duration was significantly associated with higher DQ in the language domains of GDS, and with lower scores in the approach-withdrawal and adaptability domains of CTTS, compared with the non-significant associations observed when the duration was ≥6 months (<6 months vs ≥6 months: P_{log-likelihood-ratio}-values<0.05). However, no significant differences (<6 months vs ≥6 months) were observed in the associations under appropriate/inadequate GWG. Significantly shorter breastfeeding duration was observed with increasing GWG when GWG was ≥17.5 kg. Conclusion ·GWG impacts the association between breastfeeding duration and toddler neurodevelopment. For offspring exposed to excessive maternal GWG during pregnancy, longer breastfeeding duration within 6 months or breastfeeding duration of ≥6 months is especially important for optimal neurodevelopment. GWG<17.5 kg is favorable for sustained breastfeeding.

Objective ·To evaluate endometrial receptivity in patients with hereditary thrombophilia [i.e., hereditary prethrombotic state (PTS)] and explore the therapeutic effect of low-dose aspirin (LDA) using uterine color Doppler ultrasound blood flow parameter detection. Methods ·A total of 265 patients who attended the Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2023 to December 2024 due to infertility or a history of adverse pregnancy outcomes were enrolled as research subjects. Based on the inclusion and exclusion criteria, 191 patients were finally included in the study. According to the Expert Consensus on the Diagnosis of Causes of Recurrent Miscarriage (2022 edition), the patients were divided into three groups: the hereditary PTS group (n=71), the antiphospholipid syndrome (APS) group (n=70), and the control group (n=50). Patients in the hereditary PTS and APS groups were treated with LDA continuously for 2 months, while the control group did not receive LDA treatment. The main observation indicators included uterine artery blood flow parameters [pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D)] and endometrial parameters [endometrial thickness and endometrial blood flow parameters (PI, RI, and S/D). Before LDA treatment, color Doppler ultrasound was used to detect the main observation indicators in the three groups of patients. After completing LDA treatment, patients in the hereditary PTS and APS groups underwent a second measurement. The ultrasonographic parameters of the three groups before treatment were compared to analyze the effects of hereditary PTS on endometrial thickness and blood perfusion. In addition, the ultrasonographic parameters of the hereditary PTS group and APS group before and after treatment were compared to evaluate the therapeutic efficacy of LDA. Results ·Before LDA treatment, compared with the control group, patients in the APS group and hereditary PTS group exhibited higher levels of endometrial blood flow parameters (PI, RI, S/D) and uterine artery blood flow parameters (RI, S/D) (P<0.05). After LDA treatment, patients in the hereditary PTS group showed decreases in endometrial blood flow PI, as well as uterine artery blood flow PI, RI, and S/D (P<0.05). Conclusion ·Patients with hereditary PTS have endometrial hypoperfusion, and LDA treatment can significantly improve endometrial blood flow and uterine artery perfusion in these patients, which has potential clinical value in enhancing their endometrial receptivity.

Objective ·To compare the clinical efficiency and safety of conventional treatment, recombinant human growth hormone (rhGH) monotherapy, and adenotonsillectomy combined with rhGH in children with moderate obstructive sleep apnea (OSA) and idiopathic short stature (ISS). Methods ·A total of 60 children with moderate OSA and ISS were enrolled between 2020 and 2023 in the Department of Otolaryngology Head and Neck Surgery and the Department of Endocrinology at Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine. Based on different clinical treatment regimens, the children were divided into three groups (conventional treatment group, rhGH treatment group, and adenotonsillectomy combined with rhGH treatment group), with 20 cases in each group. The dynamic changes in growth-related indicators [including height, height increase, bone age, bone age maturity, insulin-like growth factor-1 (IGF-1) level, and insulin-like growth factor-binding protein-3 (IGFBP-3) level] were analyzed among the three groups before and after treatment. In addition, clinical symptoms and therapeutic efficacy in three groups were evaluated before treatment and at 6 and 12 months post-treatment, including the obstructive apnea-hypopnea index (OAHI), minimum peripheral oxygen saturation, and Disease-Specific Quality of Life for Children with Obstructive Sleep Apnea-18 Items Survey (OSA-18). Results ·At 6 and 12 months post-treatment, the children in the rhGH treatment group showed superior improvements in height increase and growth hormone secretion (IGF-1 and IGFBP-3 levels) compared with those in the conventional treatment group. The surgery combined with rhGH treatment group also demonstrated better outcomes than the rhGH treatment group, with the differences being statistically significant (all P<0.05). After 12 months of treatment, height and bone age of the three groups of children increased compared with pre-treatment (all P<0.001), and no abnormalities in blood lipid levels or metabolism were observed. The bone age maturity of children in the surgery combined with rhGH treatment group showed a statistically significant difference compared with pre-treatment (P=0.002). In contrast, no statistically significant difference was observed in bone age maturity between the rhGH treatment group and the control group. Compared with pre-treatment levels, both the rhGH treatment group and the surgery combined with rhGH treatment group showed significant increases in IGF-1 and IGFBP-3 levels (both P<0.001); however, no statistically significant differences were observed in the control group compared with pre-treatment levels. Compared with pre-treatment levels, the OAHI and OSA-18 scores in the surgery combined with rhGH treatment group were significantly reduced, and the minimum peripheral oxygen saturation was improved, with all differences being statistically significant (all P<0.001). In contrast, no statistically significant differences were observed in these three indicators of the control group and the rhGH treatment group compared with pre-treatment levels. At 12 months, 16 children in the surgery combined with rhGH treatment group reached the standardized height growth curve (mean height of normal children of the same age and sex ±1 standard deviation), whereas only 2 children in the rhGH treatment group met this criterion. No child in the control group achieved this outcome. The differences between the surgery combined with rhGH treatment group and the rhGH treatment group, as well as between the rhGH treatment group and the control group, were statistically significant (all P<0.001). Conclusion ·In children with moderate OSA and ISS, rhGH therapy demonstrates generally acceptable metabolic safety, and adenoid-tonsillectomy combined with rhGH treatment shows significant synergistic effects in promoting height growth.

Objective ·To explore the comorbidity of depression and anxiety symptoms among college students and its correlation with social networking service addiction. Methods ·A cross-sectional questionnaire survey was conducted among undergraduate students from five colleges in Shanghai to collect the demographic characteristics of the participants, and the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder (GAD-7), and the Social Network Addiction Tendency Scale for Adolescents were used to assess the status of depression, anxiety, and social networking service addiction. Multivariate analysis of social networking service addiction among college students was conducted by using Logistic regression. Latent profile analysis was employed to categorize depression and anxiety symptoms among college students, and to identify their heterogeneity. Classification error was corrected by using the robust three-step method. The χ² test and Logistic regression analysis were employed to examine whether significant differences existed in the rates of social networking service addiction across different categories. Results ·Among the 1 768 participants enrolled in the survey, 23.53% had comorbid depression and anxiety symptoms, and 66.29% exhibited social networking service addiction. The probability of social networking service addiction in the group with comorbid depression and anxiety symptoms (n=416) was 6.093 times that of the group without depression or anxiety symptoms (n=618) (OR=6.093, 95%CI 4.426‒8.389), after adjustment for demographic factors. The probability of social networking service addiction in the group with either depression or anxiety symptoms alone (n=734) was 2.442 times that of the group without depression or anxiety symptoms (OR=2.442, 95%CI 1.947‒3.064), after adjustment for demographic factors. Latent profile analysis classified depression and anxiety symptoms into three categories: a medium-level group (45.4%), a low-level group (46.3%), and a high-level group (8.3%). There were statistically significant differences in the social networking service addiction rates among the three categories. Moreover, compared with the low-level group, the medium-level group and the high-level group had a higher risk of developing social networking service addiction (all P<0.001). Conclusion ·Depression and anxiety symptoms among college students are heterogeneous, and comorbidity is common. Students with more severe comorbid depression and anxiety symptoms also have higher levels of social networking service addiction. Greater attention should be paid to the mental health of college students, and targeted interventions should be implemented to address social networking service addiction among college students with severe symptoms of depression and anxiety.

The prevalence of non-suicidal self-injury (NSSI) among adolescents is on the rise worldwide, and an increasing number of studies indicate that the onset age tends to be younger. Therefore, it has become a public health issue of great concern to all sectors of society.Contrary to previous research perspectives, current studies suggest that NSSI behaviors can be present in various disorders, such as mood disorders, personality disorders, and substance use disorders.Research shows that individuals engaging in NSSI often have impaired social functioning, which is closely related to impaired cognitive function.Impairments in different components also suggest corresponding functional deficits. Cognitive function encompasses numerous components, mainly including attention, executive function, and learning and memory. These components are associated with the occurrence and development of NSSI to some extent.It is worth noting that the identification and assessment of NSSI behaviors have gone beyond the traditional scope of neuropsychology.In neuroimaging and neurophysiology, an increasing number of research results suggest that there are significant differences in brain function and structure between individuals with NSSI and healthy individuals. Therefore, this article systematically reviews the literature on the cognitive functional characteristics and neural mechanisms of adolescents with NSSI behaviors, aiming to provide a basis for a deeper understanding of the neurobiological basis of NSSI.

Retinopathy of prematurity (ROP) is a retinal vascular proliferative fundus disease that occurs in premature infants with low birth weight. Currently, a widely used treatment is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Ranibizumab is the only anti-VEGF drug approved by the National Medical Products Administration for the treatment of ROP in China. Ranibizumab is a humanized recombinant monoclonal antibody Fab fragment that can inhibit pathological neovascularization. A single intravitreal injection of ranibizumab is effective for active ROP lesions; but there is a high risk of recurrence, which usually requires multiple repeated injections. The long-term efficacy of ranibizumab can promote the development of retinal vascularization, but it may have certain effects on the retinal structure. Low-dose ranibizumab has been shown to achieve favorable therapeutic outcomes, which may be beneficial in improving the safety of the drug. For the safety of ranibizumab, compared with laser photocoagulation treatment, ranibizumab has a lower incidence of high myopia and structural abnormalities. However, further research is needed to evaluate its long-term systemic effects. Combination therapy with ranibizumab and supplementary laser photocoagulation, individualized treatment strategies, standardized follow-up systems, and the exploration of novel drug delivery routes are the future research directions. This article reviews the latest research on the treatment of ROP with ranibizumab, providing reference for clinical practice.

Childhood trauma serves as a significant environmental risk factor for the onset of schizophrenia, and through complex biological programming mechanisms, it increases the susceptibility of individuals to neurodevelopmental abnormalities. Anhedonia, as one of the core negative symptoms of schizophrenia, is characterized by a persistent decline in the ability to respond to pleasurable stimuli, severely affecting the social functions and long-term prognosis of patients. Recent studies have revealed that the abnormal activation of immune-inflammatory pathways may serve as a crucial intermediary link connecting childhood trauma exposure with the pathophysiological process of anhedonia in schizophrenia. Childhood trauma can lead to a systemic low-grade chronic inflammatory state by continuously activating stress- and metabolism-related physiological pathways, which in turn causes a series of immune disorders, such as elevated pro-inflammatory factors, suppressed anti-inflammatory functions, and abnormal activation of neuroimmune cells. These changes may further mediate the occurrence and development of anhedonia by affecting neural functions and circuits. This review summarizes and analyzes current research progress, systematically elaborates the impact of childhood trauma on the immune system and the potential mechanisms of anhedonia in schizophrenia, and focuses on analyzing the correlation between the two and the mediating role of immune-inflammatory factors.

Atypical depression (AD) is a subtype of depression characterized by emotional reactivity, excessive sleep, increased appetite, and interpersonal sensitivity. The prevalence of excessive sleep in AD patients is significantly higher than that in patients with typical depression. Patients have characteristics such as prolonged total sleep time, poor sleep quality, and abnormal sleep structure, which are closely related to prolongation of the disease course, increased risk of recurrence, and poor treatment response. Imbalances in neurotransmitters, elevation of inflammatory factors, and disorders of the hypothalamic-pituitary-adrenal axis are considered core pathological mechanisms related to sleep disturbance in AD. Existing diagnostic tools for AD have deficiencies, thus necessitating the integration of sleep disturbance characteristics, biomarkers, and neuroimaging findings to optimize diagnostic strategies. Given the complexity and heterogeneity of AD-related sleep disturbance in terms of clinical manifestations, pathogenesis, and treatment, in-depth research requires interdisciplinary integration and collaboration. This article reviews the clinical features, pathological mechanisms, and current treatment strategies of sleep disturbances in atypical depression.

Bone defect repair is often accompanied by inadequate vascularization and persistent hypoxia, which restrict cell survival, hinder angiogenesis, and ultimately impair osteogenesis, thereby posing a major challenge to effective bone regeneration. To overcome these limitations, hydrogel systems designed to modulate the local oxygen microenvironment have attracted increasing attention in bone tissue engineering. Owing to their favorable biocompatibility, injectability, and three-dimensional network architectures, these systems incorporate peroxide-based oxygen generators, perfluorocarbon oxygen carriers, and enzyme- or nanozyme-mediated oxygen-producing modules, enabling controlled, sustained, or microenvironment-responsive oxygen release while partially mitigating oxidative stress. This review summarizes recent advances in oxygen-releasing hydrogels, with an emphasis on hydrogel matrix selection, oxygen sources and loading strategies, and the regulation of oxygen release kinetics. The biological mechanisms underlying their pro-regenerative effects are further discussed, including the alleviation of local hypoxia, promotion of angiogenesis and osteogenic differentiation, and modulation of inflammatory responses and the immune microenvironment. Experimental evidence indicates that these hydrogel systems can substantially improve the quality of newly formed bone and enhance repair efficiency in calvarial and other small-animal bone defect models. Importantly, emerging studies suggest that successful bone regeneration depends not simply on increasing oxygen availability, but on achieving an appropriate balance among oxygen release intensity, duration, and the stage-specific requirements of bone repair. Future work should therefore prioritize quantitative control of oxygen release kinetics, long-term biosafety, and stability in complex pathological microenvironments to advance clinical translation.

Objective ·To analyze the clinical, imaging, and genetic characteristics of spastic paraplegia (SPG) phenotypes caused by amyotrophic lateral sclerosis (ALS)-related genes. Methods ·A total of 5 pedigrees with SPG caused by ALS-related genes, admitted to the Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, from April 2017 to September 2025, were included in the study. Detailed medical histories and imaging examinations were collected, and Sanger sequencing, family co-segregation verification, and phenotype analyses were performed. Results ·Among the 5 probands, the male-to-female ratio was 3:2. The average age at onset was (18.4±21.7) years (ranging from 1 to 51 years), and the average disease duration was (12.8±13.3) years (ranging from 3 to 33 years). Physical examination revealed increased muscle tone in the lower extremities in all patients (5/5), hyperreflexia in the lower extremities (5/5), patellar clonus in 2 patients (2/5), ankle clonus in 4 patients (4/5), positive pathological signs in the lower extremities in 4 patients (4/5), and foot deformities in 2 patients (2/5). Brain MRI examinations detected abnormalities in 2 patients, specifically cerebellar and cervical spinal cord atrophy in case 1, and a small number of abnormal signals in the splenium of the corpus callosum in case 2. Peripheral nerve electrophysiological examinations indicated that a small number of spontaneous potentials were observed in both lower extremities of 1 patient, and motor evoked potentials revealed central conduction impairment. Genetic testing identified pathogenic variants in 4 different genes, namely amyotrophic lateral sclerosis 2 (ALS2), valosin-containing protein (VCP), senataxin (SETX), and never in mitosis gene A-related kinase 1 (NEK1), in these 5 patients. Among them, 2 new variants, c.3527T>C (p.Met1176Thr) and c.1732T>C (p.Ser578Pro), were newly discovered in the ALS2 gene. Conclusion ·This article analyzes the clinical heterogeneity and genetic characteristics of SPG patients caused by ALS-related genes, providing clinical evidence for accurate diagnosis and in-depth understanding of such diseases.